This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The aim of this proposal is to discover and develop novel anti-infective agents utilizing a natural product core-based library approach. Historically, natural products are known as a rich source of compounds found to be bioactive against a wide range of disease states, in particular as anti-infective drugs or as lead compounds. Specific Aim 1. Further optimization and development of nucleoside peptide anti-tuberculosis agents. We would like to develop nucleoside peptide mimics as novel anti-tuberculosis agents targeting cell wall biosynthesis. To achieve this goal, we aim to design and synthesize a small focused optimization library based on the hits from our primary screens of a nucleoside peptide discovery library that has great structural similarity to the Mureidomycins. Specific Aim 2. Design and synthesis of Gallinamide A analogs as potential antimalarial agents. The purpose of this aim is to develop a feasible synthesis that allows rapid access to Gallinamide A analogs for antimalarial screening. To achieve this goal, we will again use a library core based approach to design and synthesize a diversity oriented library based on a Gallinamide A template.